This invention relates to a device for agitating fluids, specifically for use with automatic pipetting equipment. The invention is particularly useful for agitation of stratified fluids and for maintaining uniformity of solid-fluid suspensions.
Many laboratory processes employ materials requiring agitation or stirring to obtain or maintain desired properties. Such materials may include suspensions of solid particulate matter in a fluid and mixtures of insoluble fluids. When the constituents of the material have different densities, settling can occur. Laboratories frequently use automated pipetting devices to withdraw samples of such materials from a reservoir. These pipetting devices insert an array (usually rectangular) of pipette tips into the reservoir then aspirate samples of the material into the pipette tips for deposit elsewhere. The material in each sample at each withdrawal must have a known and controlled concentration of the constituents of the material. Therefore, it may be necessary to continuously agitate the material.
In the prior art, numerous varied methods for agitation are described. These prior methods have certain disadvantages for use with automated pipetting equipment:
1) Manual agitation, by shaking the reservoir or using a stirring rod, has the disadvantage of requiring human attention and diligence, which may result in spillage, contamination, inconsistent agitation, interference with the automated equipment, or exposure of people to hazardous materials. PA1 2) Circulation using a pump requires fluid inlets and outlets to the reservoir and requires a pump which may be relatively complex and subject to local accumulation of particulate. The pump may thus be subject to dogging or other failure and may require frequent flushing. In addition, the pump system likely has seals and fittings that may leak Also, it may be difficult to avoid "dead spots" within the reservoir where circulation does not occur, allowing settling of particulate. PA1 3) Rotary stirrers (for example, magnetic stirrers by Cole-Parmer Instrument Company of Niles, Ill. or that described in U.S. Pat. No.5,834,739 (1998) to Lockwood, et al.) are effective for stirring solutions in mixing chambers having axial symmetry, such as beakers. However, rotary stirrers are not well adapted to use in rectangular reservoirs that receive pipette tips. Centrifugal effects cause a vortex, where the fluid level in the reservoir to vary from low near the stirring element to high near the edges of the reservoir, possibly causing pipettes to draw air. Also, given the differing densities of the components of the mixture, the stirrer may act as a centrifuge, increasing the concentration of denser materials at increasing distances from the stirrer. It may be impractical to locate a continuously rotating stirrer in a standard reservoir without physically interfering with the pipette tips. PA1 4) U.S. Pat. No. 4,477,192 (1984) to Bonney describes a magnetic stirrer in which the stirring element moves erratically within a mixing chamber. If used with pipetting equipment, the stirring element will tend to interfere with the pipette tips, or vice versa. PA1 5) Agitation of the entire reservoir (using, for example, a laboratory platform shaker) may require that the reservoir be mechanically fixed to the agitator, a disadvantage for convenient movement or replacement of the reservoir. The magnitude of the agitation is limited to the point where fluid spills or splashes from the open-topped reservoir, and to the extent where the motion interferes with the operation of pipetting equipment. PA1 6) Agitation may be achieved by imparting motion to the fluid via elastic deformation of some portion of the interior surface of the reservoir. U.S. Pat. No. 4,793,714 (1988) to Gruber discloses a mixer which employs a vibrating membrane on some wall of the mixing chamber. U.S. Pat. No. 4,232,972 (1980) to Levin discloses a mixer here the walls and bottom of the chamber are deformed to impart impulses to the fluid These methods require a purpose-built mixing chamber, which is disadvantageous compared to using simple, disposable, standard reservoirs. PA1 7) U.S. Pat. No. 5,736,100 (1998) to Miyake et al., discloses a method for mixing by imparting ultrasonic waves into the material to be mixed. Unless very carefully directed and controlled, ultrasonic mixing produces highly localized agitation, which may not produce consistent mixture and which may cause splashing and undesired heating. PA1 8) U.S. Pat. No. 5,443,791 (1995) to Cathcart et al. (column 9, line 33 and column 36, line 11) describes a method for stirring using the pipetting device itself. The pipette tips repeatedly aspirate and dispense the fluid in the reservoir and may be moved within the reservoir to achieve mixing. This method requires that the pipettes spend extra time within the reservoir to effect mixing. In addition, the pipette tips may be required to make extra trips to the reservoir to prevent settling even when no sample from that reservoir is immediately needed. PA1 9) HyperTask of Hopkinton, Mass. markets a mixer for use in a reservoir with automated pipetting equipment. In this device, a mixing paddle reciprocates horizontally within the reservoir. This horizontal motion allows pipetting from only one end of the reservoir, preventing the use of a complete array of pipettes. PA1 10) U.S. Pat. No. 5,100,242 (1992) to Latto discloses a mixing method in which an orifice plate is reciprocated within a fluid at right angles to the plane of the plate to generate vortex rings. The disclosure specifies a range of ratios of motion amplitude to orifice diameter. The present invention is not constrained to operate within that range, nor is it constrained to use circular holes. In addition, the disclosure specifies that to generate effective ring vortices, the minimum distance from the center of an orifice to the edge of the orifice plate or to the edge of another orifice is twice the diameter of the orifice. The present invention is not so constrained, and in fact, in the preferred embodiment, the present invention's orifices are doser together than Latto specifies. In short, the present invention is not a ring vortex mixer. PA1 (a) to provide agitation of fluid mixtures in a reservoir without requiring regular participation or attention from a human operator; PA1 (b) to provide a well controlled, uniform fluid mixture in a reservoir; PA1 (c) to provide continuous agitation in a reservoir without impeding or interfering with the insertion of a complete array of pipettes into the reservoir; PA1 (d) to provide agitation with an agitating element that is simple in configuration and is easy to clean or replace; PA1 (e) to provide agitation with minimal risk of contamination, spillage, or leakage; PA1 (f) to provide agitation in standard reservoirs, maintaining compatibility with typical laboratory equipment; PA1 (g) to provide agitation without requiring the automated pipetting device to spend extra time or make extra trips to the reservoir; and PA1 (h) to provide agitation in an open-topped reservoir without splashing or excess sloshing.